The Role of Cystathionine-γ-lyase in Blunt Chest Trauma in Cigarette Smoke Exposed Mice

Clair Hartmann, Sebastian Hafner, Angelika Scheuerle, Peter Möller, Markus Huber-Lang, Birgit Jung, Benedikt Nubaum, Oscar McCook, Michael Gröger, Florian Wagner, Sandra Weber, Bettina Stahl, Enrico Calzia, Michael Georgieff, Csaba Szabo, Rui Wang, Peter Radermacher, Katja Wagner

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    ABSTRACT: Pre-traumatic cigarette smoke (CS) exposure aggravates post-traumatic acute lung injury (ALI). Cystathionine-γ-lyase (CSE) protects against ALI and CS exposure-induced chronic obstructive lung disease (COPD). Therefore, we tested the hypothesis whether genetic CSE knockout (CSE) would aggravate post-traumatic ALI after CS exposure. After 3–4 weeks of CS exposure, anesthetized wild type (WT) and CSE mice underwent blunt chest trauma, surgical instrumentation and 4?hours of lung-protective mechanical ventilation. We measured hemodynamics, lung mechanics, gas exchange, metabolism and acid-base status together with blood and tissue cytokine and chemokine levels, tissue expression of mediator proteins, parameters of oxidative and nitrosative stress, and histology. CSE mice without CS exposure, showed higher cytokine and chemokine levels, and this was further enhanced by CS exposure, particularly in males. CS exposure in WT mice aggravated post-traumatic alveolar membrane thickening, dystelectasis and inflammatory cell accumulation, which was associated with higher thoracopulmonary compliance. Pre-traumatic CS exposure in CSE mice produced a similar response, except for less alveolar membrane thickening, most likely due to lung hyperinflation. CS-exposed WT mice showed the most pronounced metabolic acidosis, while CS exposure in CSE mice resulted in the lowest blood glucose levels. Urinary output and anesthesia rate were highest in male CS-exposure CSE animals. In conclusion, in murine acute-on-chronic pulmonary disease, CSE knockout aggravated post-traumatic inflammation, which was further worsened upon pre-traumatic CS exposure, and this effect was particularly pronounced in males. Hence, maintaining CSE expression is critically important for stress adaptation during ALI and CS-induced COPD, most likely in a gender-dependent manner.

    Original languageEnglish (US)
    JournalShock
    DOIs
    StateAccepted/In press - Sep 28 2016

    Fingerprint

    Cystathionine
    Lyases
    Smoke
    Tobacco Products
    Thorax
    Wounds and Injuries
    Acute Lung Injury
    Chronic Obstructive Pulmonary Disease
    Chemokines
    Lung
    Cytokines
    Membranes
    Acidosis
    Mechanics
    Artificial Respiration

    ASJC Scopus subject areas

    • Emergency Medicine
    • Critical Care and Intensive Care Medicine

    Cite this

    Hartmann, C., Hafner, S., Scheuerle, A., Möller, P., Huber-Lang, M., Jung, B., ... Wagner, K. (Accepted/In press). The Role of Cystathionine-γ-lyase in Blunt Chest Trauma in Cigarette Smoke Exposed Mice. Shock. https://doi.org/10.1097/SHK.0000000000000746

    The Role of Cystathionine-γ-lyase in Blunt Chest Trauma in Cigarette Smoke Exposed Mice. / Hartmann, Clair; Hafner, Sebastian; Scheuerle, Angelika; Möller, Peter; Huber-Lang, Markus; Jung, Birgit; Nubaum, Benedikt; McCook, Oscar; Gröger, Michael; Wagner, Florian; Weber, Sandra; Stahl, Bettina; Calzia, Enrico; Georgieff, Michael; Szabo, Csaba; Wang, Rui; Radermacher, Peter; Wagner, Katja.

    In: Shock, 28.09.2016.

    Research output: Contribution to journalArticle

    Hartmann, C, Hafner, S, Scheuerle, A, Möller, P, Huber-Lang, M, Jung, B, Nubaum, B, McCook, O, Gröger, M, Wagner, F, Weber, S, Stahl, B, Calzia, E, Georgieff, M, Szabo, C, Wang, R, Radermacher, P & Wagner, K 2016, 'The Role of Cystathionine-γ-lyase in Blunt Chest Trauma in Cigarette Smoke Exposed Mice', Shock. https://doi.org/10.1097/SHK.0000000000000746
    Hartmann, Clair ; Hafner, Sebastian ; Scheuerle, Angelika ; Möller, Peter ; Huber-Lang, Markus ; Jung, Birgit ; Nubaum, Benedikt ; McCook, Oscar ; Gröger, Michael ; Wagner, Florian ; Weber, Sandra ; Stahl, Bettina ; Calzia, Enrico ; Georgieff, Michael ; Szabo, Csaba ; Wang, Rui ; Radermacher, Peter ; Wagner, Katja. / The Role of Cystathionine-γ-lyase in Blunt Chest Trauma in Cigarette Smoke Exposed Mice. In: Shock. 2016.
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    abstract = "ABSTRACT: Pre-traumatic cigarette smoke (CS) exposure aggravates post-traumatic acute lung injury (ALI). Cystathionine-γ-lyase (CSE) protects against ALI and CS exposure-induced chronic obstructive lung disease (COPD). Therefore, we tested the hypothesis whether genetic CSE knockout (CSE) would aggravate post-traumatic ALI after CS exposure. After 3–4 weeks of CS exposure, anesthetized wild type (WT) and CSE mice underwent blunt chest trauma, surgical instrumentation and 4?hours of lung-protective mechanical ventilation. We measured hemodynamics, lung mechanics, gas exchange, metabolism and acid-base status together with blood and tissue cytokine and chemokine levels, tissue expression of mediator proteins, parameters of oxidative and nitrosative stress, and histology. CSE mice without CS exposure, showed higher cytokine and chemokine levels, and this was further enhanced by CS exposure, particularly in males. CS exposure in WT mice aggravated post-traumatic alveolar membrane thickening, dystelectasis and inflammatory cell accumulation, which was associated with higher thoracopulmonary compliance. Pre-traumatic CS exposure in CSE mice produced a similar response, except for less alveolar membrane thickening, most likely due to lung hyperinflation. CS-exposed WT mice showed the most pronounced metabolic acidosis, while CS exposure in CSE mice resulted in the lowest blood glucose levels. Urinary output and anesthesia rate were highest in male CS-exposure CSE animals. In conclusion, in murine acute-on-chronic pulmonary disease, CSE knockout aggravated post-traumatic inflammation, which was further worsened upon pre-traumatic CS exposure, and this effect was particularly pronounced in males. Hence, maintaining CSE expression is critically important for stress adaptation during ALI and CS-induced COPD, most likely in a gender-dependent manner.",
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    AU - Hafner, Sebastian

    AU - Scheuerle, Angelika

    AU - Möller, Peter

    AU - Huber-Lang, Markus

    AU - Jung, Birgit

    AU - Nubaum, Benedikt

    AU - McCook, Oscar

    AU - Gröger, Michael

    AU - Wagner, Florian

    AU - Weber, Sandra

    AU - Stahl, Bettina

    AU - Calzia, Enrico

    AU - Georgieff, Michael

    AU - Szabo, Csaba

    AU - Wang, Rui

    AU - Radermacher, Peter

    AU - Wagner, Katja

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    N2 - ABSTRACT: Pre-traumatic cigarette smoke (CS) exposure aggravates post-traumatic acute lung injury (ALI). Cystathionine-γ-lyase (CSE) protects against ALI and CS exposure-induced chronic obstructive lung disease (COPD). Therefore, we tested the hypothesis whether genetic CSE knockout (CSE) would aggravate post-traumatic ALI after CS exposure. After 3–4 weeks of CS exposure, anesthetized wild type (WT) and CSE mice underwent blunt chest trauma, surgical instrumentation and 4?hours of lung-protective mechanical ventilation. We measured hemodynamics, lung mechanics, gas exchange, metabolism and acid-base status together with blood and tissue cytokine and chemokine levels, tissue expression of mediator proteins, parameters of oxidative and nitrosative stress, and histology. CSE mice without CS exposure, showed higher cytokine and chemokine levels, and this was further enhanced by CS exposure, particularly in males. CS exposure in WT mice aggravated post-traumatic alveolar membrane thickening, dystelectasis and inflammatory cell accumulation, which was associated with higher thoracopulmonary compliance. Pre-traumatic CS exposure in CSE mice produced a similar response, except for less alveolar membrane thickening, most likely due to lung hyperinflation. CS-exposed WT mice showed the most pronounced metabolic acidosis, while CS exposure in CSE mice resulted in the lowest blood glucose levels. Urinary output and anesthesia rate were highest in male CS-exposure CSE animals. In conclusion, in murine acute-on-chronic pulmonary disease, CSE knockout aggravated post-traumatic inflammation, which was further worsened upon pre-traumatic CS exposure, and this effect was particularly pronounced in males. Hence, maintaining CSE expression is critically important for stress adaptation during ALI and CS-induced COPD, most likely in a gender-dependent manner.

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